ANP32A regulates ATM expression and prevents oxidative stress in cartilage, brain, and bone

Cornelis, F.M.; Monteagudo, S.; Guns, Laura-An; Hollander, Wouter den; Nelissen, Rob G H H; Storms, L.; Peeters, Tine; Jonkers, Ilse; Meulenbelt, Ingrid; Lories, Rik

doi:10.1126/scitranslmed.aar8426

Cited by 28 publications

(50 citation statements)

References 77 publications

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“…ANP32A is implicated in neurons differentiation, brain development, and neuritogenesis. Modulating ANP32A signaling could help manage oxidative stress in brain [67] and restore cognitive function [68] with therapeutic implications for neurological disease. To our best knowledge, no study has reported therole of RUNX1-IT1 and ANP32A-IT1 in stroke.…”

Section: Discussionmentioning

confidence: 99%

Hub Genes of Stroke Identified by Weighted Gene Co-expression Network Analysis

Zhai

et al. 2020

Preprint

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BACKGROUD: Microarray-based gene expression profiling is widely used in biomedical research. Weighted gene co-expression network analysis (WGCNA) links microarray data directly to clinical traits and identifies rules for predicting pathological stage and prognosis of disease.WGCNA is useful in understandingmany biological processes. Stroke is a common disease worldwide, however, molecular mechanisms of its pathogenesis are largely unknown. The aim of this study was to construct gene co-expression networks for identification of key modules and hub genes associated with stroke pathogenesis.METHODS: Gene microarray expression profiles of stroke samples were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were screened by the limma package in R software. WGCNA was used to construct free-scale gene co-expression networks to explore the associations between gene sets and clinical features, and to identify key modules and hub genes. Subsequently, functional enrichment analyses were performed. Further, receiver operating characteristic (ROC) curve analysis was carried out to validate expression of hub genes and literature validation was performed as well.RESULTS: A total of 11,747 most variant genes were used for co-expression network construction. Pink and yellow modules were significantly correlated to stroke pathogenesis. Functional enrichment analysis showed that the pink module was mainly involved in regulation of neuron regeneration, and repair of DNA damage.On the other hand, yellow module was mainly enriched in ion transport system dysfunction which was correlated with neuron death. A total of eight hub genes (PRR11, NEDD9, Notch2, RUNX1-IT1, ANP32A-IT1, ASTN2, SAMHD1 and STIM1) were identified and validated at transcriptional levels and through existing literature.CONCLUSION: The eight hub genes (PRR11, NEDD9, Notch2, RUNX1-IT1, ANP32A-IT1, ASTN2, SAMHD1 and STIM1) identified in the study are potentialbiomarkers and therapeutic targets for effective diagnosis and treatment of stroke.

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Section: Discussionmentioning

confidence: 99%

Hub Genes of Stroke Identified by Weighted Gene Co-expression Network Analysis

Zhai

et al. 2020

Preprint

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“…Consistently, clinical and preclinical OA studies indicated a cumulative oxidative burden in osteoarthritic chondrocytes 39,40 . Emerging evidence suggests that oxidative stress plays a significant role in OA development and the disease progression can be mitigated by counteracting oxidative stress 36,[84][85][86] . In general, oxidative stress results from the abnormal production of ROS and the loss of cellular antioxidant capacity.…”

Section: Physiological Significance Of Oxidative Stress In Chondrocytesmentioning

confidence: 99%

“…In addition, ROS induce matrix degeneration through the upregulation of matrix-degrading enzyme expression while this effect is abolished by antioxidant treatment 123,125 . The detrimental effects of ROS on cartilage homeostasis can be effectively alleviated by augmenting cellular antioxidant activity under stress conditions, and several attempts have been made to treat OA by targeting the regulators involved in oxidative stress production in cartilage [84][85][86] .…”

Section: Antioxidant Defense and Redox Homeostasismentioning

confidence: 99%

The role of selenium metabolism and selenoproteins in cartilage homeostasis and arthropathies

Kang

Lee

et al. 2020

Exp Mol Med

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As an essential nutrient and trace element, selenium is required for living organisms and its beneficial roles in human health have been well recognized. The role of selenium is mainly played through selenoproteins synthesized by the selenium metabolic system. Selenoproteins have a wide range of cellular functions including regulation of selenium transport, thyroid hormones, immunity, and redox homeostasis. Selenium deficiency contributes to various diseases, such as cardiovascular disease, cancer, liver disease, and arthropathy—Kashin–Beck disease (KBD) and osteoarthritis (OA). A skeletal developmental disorder, KBD has been reported in low-selenium areas of China, North Korea, and the Siberian region of Russia, and can be alleviated by selenium supplementation. OA, the most common form of arthritis, is a degenerative disease caused by an imbalance in matrix metabolism and is characterized by cartilage destruction. Oxidative stress serves as a major cause of the initiation of OA pathogenesis. Selenium deficiency and dysregulation of selenoproteins are associated with impairments to redox homeostasis in cartilage. We review the recently explored roles of selenium metabolism and selenoproteins in cartilage with an emphasis on two arthropathies, KBD and OA. Moreover, we discuss the potential of therapeutic strategies targeting the biological functions of selenium and selenoproteins for OA treatment.

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“…Isolated articular chondrocytes from several pups from the same litter were pooled, sample #1 is one pooled litter and sample #2 is a pool from another different litter. RNA was isolated using and cDNA synthesis was performed as previously described [31]. Next, real-time qPCR was performed with primers specific for mice C1QA/B/C, C1R and C1S (see Table 2 for primer sequences).…”

Section: Qpcr Mouse Chondrocytesmentioning

confidence: 99%

Complement component C1q is produced by isolated articular chondrocytes

Lubbers

Schaarenburg

Kwekkeboom

et al. 2020

Osteoarthritis and Cartilage

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Objective: Inflammation and innate immune responses may contribute to development and progression of Osteoarthritis (OA). Chondrocytes are the sole cell type of the articular cartilage and produce extracellular-matrix molecules. How inflammatory mediators reach chondrocytes is incompletely understood. Previous studies have shown that chondrocytes express mRNA encoding complement proteins such as C1q, suggesting local protein production, which has not been demonstrated conclusively. The aim of this study is to explore C1q production at the protein level by chondrocytes. Design: We analysed protein expression of C1q in freshly isolated and cultured human articular chondrocytes using western blot, ELISA and flow cytometry. We examined changes in mRNA expression of collagen, MMP-1 and various complement genes upon stimulation with proinflammatory cytokines or C1q. mRNA expression of C1 genes was determined in articular mouse chondrocytes. Results: Primary human articular chondrocytes express genes encoding C1q, C1QA, C1QB, C1QC, and secrete C1q to the extracellular medium. Stimulation of chondrocytes with pro-inflammatory cytokines upregulated C1QA, C1QB, C1QC mRNA expression, although this was not confirmed at the protein level. Extracellular C1q bound to the chondrocyte surface in a dose dependent manner. In a pilot study, binding of C1q to chondrocytes resulted in changes in the expression of collagens with a decrease in collagen type 2 and an increase in type 10. Mouse articular chondrocytes also expressed C1QA, C1QB, C1QC, C1R and C1S at the mRNA level. Conclusions: C1q protein can be expressed and secreted by human articular chondrocytes and is able to bind to chondrocytes impacting collagen expression.

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ANP32A regulates ATM expression and prevents oxidative stress in cartilage, brain, and bone

Cited by 28 publications

References 77 publications

Hub Genes of Stroke Identified by Weighted Gene Co-expression Network Analysis

Hub Genes of Stroke Identified by Weighted Gene Co-expression Network Analysis

The role of selenium metabolism and selenoproteins in cartilage homeostasis and arthropathies

Complement component C1q is produced by isolated articular chondrocytes

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